Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.1112
Peer-review started: March 13, 2023
First decision: May 12, 2023
Revised: May 17, 2023
Accepted: May 30, 2023
Article in press: May 30, 2023
Published online: July 15, 2023
As the growing amount of information consolidated in the field of glucocorticoids’ (GCs) hyperglycemia effect, whether GCs replacement therapy disturbs glycometabolism homeostasis in patients with hypopituitarism has garnered considerable interest. Timely and adequate GCs replacement has been commonly recognized as a lifesaving prescription for those patients with hypopituitarism, which aims to restore hormone deficiency and improve well-being. Choosing an optimum GCs replacement regimen for patients with hypopituitarism continues to be challenging problem as the physiological cortisol rhythm is difficult to replicate. An inability to mimic physiological cortisol rhythms or over-treatment may make those patients receiving GCs replacement susceptible to metabolic disturbances and subsequent cardiovascular events.
Commonly used glucocorticoids replacement regimens in hypopituitarism patients have difficulty mimicking physiological cortisol rhythms and are usually accompanied with risks of over-treatment, which will pose adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. As the increasing prevalence of adverse events occurs in hypopituitarism patients under GCs replacement, greater emphasis has been placed on choosing a suitable replacement regimen with as little influence on glycometabolism as possible.
This study was designed to assess the glucose metabolism profile recorded by a flash glucose monitoring system in patients with hypopituitarism, illuminating the impact of GCs preparation (Pred) and prescription doses on glucose metabolism. In doing so, we hope to add novel insights into the existing body of evidence and provide references to guide the treatment choices for those patients with hypopituitarism, in order to reduce the incidence of cardiovascular events.
In this study, patients with hypopituitarism treated with Pred were enrolled as patient group (PG), and regrouped into Pred > 5 mg/d group and Pred ≤ 5 mg/d group based on the recommended Pred dose per day. Age- and sex-matched normal controls (NCs) without known hypopituitary dysfunction or glycometabolic disorders were enrolled. At baseline, all the recruited patients underwent hypopituitary-adrenal/thyroid function assessment, along with electrolyte and glucose metabolism evaluation, including plasma sodium, glycosylated hemoglobin, fasting blood glucose, and fasting insulin. The NCs received laboratory tests similar to those of PG. Flash glucose monitoring system (FGMS) was used to record glucose profile of both PG and the NCs. Parameters of glucose-target-rate, glucose variability (GV), and period glucose level were analyzed. β-cell function and insulin resistance (IR) were assessed by calculating the homeostasis model assessment (HOMA)-β along with HOMA-IR, fasting glucose/insulin ratio, and quantitative insulin sensitivity check index.
Twenty patients diagnosed with hypopituitarism receiving Pred replacement were enrolled in this study. Of these, twelve patients were treated with doses of > 5 mg/d Pred and eight patients were treated with doses of ≤ 5 mg/d. Significantly decreased glucose-target-rate and glucose level at nocturnal period, along with increased GV, hypoglycemia occurrence, and glucose level at postprandial phase were identified in PG when compared with those of NCs. These results demonstrated that glucose metabolism homeostasis was perturbed in patients with hypopituitarism receiving Pred replacement, despite careful administration. This disturbance may carry a risk of leading to cardiovascular diseases. A dose of > 5 mg/d Pred was associated with a notable reduction in glucose-target-rate and glucose level at nocturnal period, along with elevation in GV, hypoglycemia occurrence, and glucose level at postprandial phase. However, only glucose level at 3-8 am period was changed significantly in Pred ≤ 5 mg/d group. Accordingly, we concluded that a dose of > 5 mg/d Pred may have a more adverse impact on glucose metabolism. Impaired β-cell function was indicated by relevant parameters in PG when compared to that of NCs.
Pred replacement in patients with hypopituitarism impaired glucose metabolism, leading to an increased risk of cardiovascular events. A dose of > 5 mg/d Pred had a more significant influence on glucose metabolism than a dose of ≤ 5 mg/d. A suitable Pred replacement regimen necessitates comprehensive and accurate evaluation, for which FGMS is a kind of promising and reliable assessment device. Altogether, the integration of results in this study adds weight to the existing knowledge, and further provides new reference and guidance for future clinical work to effectively avoid the risk of cardiovascular events and improve well-being in patients with hypopituitarism.
The integration of results in this study adds weight to the existing knowledge, and further provides new reference and guidance for future clinical work to effectively avoid the risk of cardiovascular events and improve well-being in patients with hypopituitarism.